Neural Circuits and Behavior
Principal Investigator: Alexander FLEISCHMANN, CR1 Inserm
Our goal is to understand how neural circuits generate sensory perception and behavior. To address this question we use a combination of molecular genetic, in vivo imaging, computational and behavioral approaches, and we focus our efforts on determining fundamental functional properties of neural networks in the mouse olfactory cortex.
A central question in neuroscience is how sensory stimuli are detected and processed by neural circuits in the brain to generate sensory perception and behavior. Our laboratory has recently developed new molecular genetic and viral approaches that allow us to target and manipulate defined neural cell types in the olfactory cortex of mice. Furthermore, we have identified, using in vivo two-photon microscopy, electrophysiological recordings and computational approaches, fundamental principles of odor information coding in cortical neural networks. These recent advances open up new opportunities to explore how diverse neural cell types contribute to odor information coding in the cortex, and how this information is transmitted to downstream target areas involved in sensory integration, cognition, and motor control. Finally, we are interested in how learning and experience alter olfactory neural network functions and behavior.
The olfactory system of mice provides a simple, tractable model system of outstanding ethological importance. Furthermore, olfactory neural circuits are particularly vulnerable to aging and neurodegenerative disease, thus representing a highly relevant experimental model system for clinical and translational neuroscience research.
Figure 1. Expression of the layer-specific genes in neocortex and olfactory cortex.
(Left) Coronal section of the adult mouse brain. (Right) Immunohistochemical analysis of Cux1 and Ctip2 expression in neocortex (top) and olfactory (piriform) cortex (bottom). Note that superficial and deep layer-specific gene expression patterns are reversed, and that in contrast to neocortex, Cux1 and Ctip2 are co-expressed in a subpopulation of piriform neurons (insert, in yellow). Cux1 and Ctip2 specify piriform neurons projecting to the olfactory bulb and the medial prefrontal cortex (for details, see Diodato et al., Nature. Comm., 2016).
Figure 2. Two-photon in vivo imaging of mitral cell odor responses in the olfactory bulb.
(A) Schematic of rabies-GCaMP3 injection into the lateral olfactory tract (LOT) and two-photon calcium imaging of olfactory bulb mitral cells. (B) Two-photon micrograph showing GCaMP3 expression in mitral cell of a single imaging site. Scale bar = 30µM. (C) Example traces of the responses of 4 mitral cells (circled in (B)) to 4 different odorants. Traces represent responses to 4 individual odorant exposures, non-responsive trials are shown in grey, responsive trials in black. Horizontal bar indicates odorant application.
- Diodato, A., Ruinart de Brimont, M., Yim, Y.S., Derian, N., Perrin, S., Pouch, J., Klatzmann, D., Garel, S., Choi, G.B. & Fleischmann, A. (2016), Molecular signatures of neural connectivity in the olfactory cortex. Nat Commun 7, 12238.
- Roland, B., Jordan, R., Sosulski, D.L., Diodato, A., Fukunaga, I., Wickersham, I., Franks, K.M., Schaefer, A.T. & Fleischmann, A. (2016), Massive normalization of olfactory bulb output in mice with a “monoclonal nose.” Elife 5, May 13;5. pii: e16335.
- Abdus-Saboor, I., Al Nufal, M.J., Agha, M.V., Ruinart de Brimont, M., Fleischmann, A. & Shykind, B.M. (2016), An Expression Refinement Process Ensures Singular Odorant Receptor Gene Choice. Curr. Biol. 26, 1083–1090.
- Abdus-Saboor I., Fleischmann A. & Shykind B. (2014), Setting Limits: Maintaining order in a large gene family. Transcription 5, e28978.
- Fleischmann A., Abdus-Saboor I., Sayed A. & Shykind B (2013), Functional Interrogation of an Odorant Receptor Locus Reveals Multiple Axes of Transcriptional Regulation. PLoS Biol 11(5): e1001568.
- Angelo K., Pimentel D., Pichler B., Fleischmann A., Rancz E. & Margrie T. (2012), A biophysical signature of network affiliation and sensory processing in mitral cells. Nature, Aug16;488(7411):375-8.
- Glinka M.E., Samuels B.A., Teillon J., Mei D.F., Shykind B.M., Hen R. & Fleischmann A. (2012), Olfactory deficits cause anxiety-like behaviors in mice. J. Neurosci., 32(19):6718-6725
- Choi G.B., Stettler D.D., Kallman B.R., Bhaskar S.T., Fleischmann A. & Axel R. (2011), Driving opposing behaviors with ensembles of piriform neurons. Cell 146:1004-1015
- Fleischmann A., Shykind B.M., Sosulski D.L., Franks K.M, Glinka M.E., Mei D.F., Yonghua S., Kirkland J., Mendelsohn M., Albers M.W. & Axel R. (2008), Mice with a "monoclonal" nose: perturbations in an olfactory map impair odor discrimination. Neuron. Dec 26; (60):1-14.
- Fleischmann A., Jochum W., Eferl R., Witowsky J. & Wagner E.F. (2003), Rhabdomyosarcoma development in mice lacking Trp53 and Fos: tumor suppression by the Fos protooncogene. Cancer Cell. Dec;4(6):477-82.
- Fleischmann A., Hvalby O., Jensen V., Strekalova T., Zacher C., Layer L.E., Kvello A., Reschke M., Spanagel R., Sprengel R., Wagner E.F. & Gass P. (2003), Impaired long-term memory and NR2A-type NMDA receptor-dependent synaptic plasticity in mice lacking c-Fos in the CNS. J Neurosci. Oct 8;23(27):9116-22.
Postdoctoral fellows & PhD Students:
Mena Wilson, Postdoctoral fellow
Vieira Inès, PhD student
Meissner-Bernard Claire, PhD student
Master Students (M1-M2):
Simon Daste (2017)
Agatha Anet (2017)
Dmitri Bryzgalov (2017)